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Development of multi-functionalized synthon for the synthesis of bioactive natural products

Research Project

Project/Area Number 18590011
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Chemical pharmacy
Research InstitutionHealth Sciences University of Hokkaido

Principal Investigator

ISHIKURA Minoru  Health Sciences University of Hokkaido, 薬学部, 教授 (10146011)

Co-Investigator(Kenkyū-buntansha) 山田 康司  北海道医療大学, 薬学部, 講師 (80272962)
阿部 匠  北海道医療大学, 薬学部, 助教 (80453273)
蓮沼 美也子  北海道医療大学, 薬学部, 助手 (50364253)
Project Period (FY) 2006 – 2008
Project Status Completed (Fiscal Year 2008)
Budget Amount *help
¥4,020,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥420,000)
Fiscal Year 2008: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2007: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2006: ¥2,200,000 (Direct Cost: ¥2,200,000)
Keywordsインドリルボレート / ビシクロラクタム / インドールアルカロイド / クロスカップリング反応 / パラジウム触媒 / セロトニン / アゼピノインドールアルカロイド / ABH / アリール化反応 / ホウ素化合物 / インドール誘導体 / クロスカップリング / マイクロウェーブ / 付加環化反応 / ビシクロアミド(ABH)
Research Abstract

多機能な化学反応性を有する合成中間体を基盤とする合成法を開発することは、多様な化学構造を有する生理活性物質の合成を行ううえで有用な方法論となる。本研究では、インドリルボレートとビシクロラクタムであるABHの合成中間体としての有用性に着目し、その応用性の開発をすすめた。この結果、重要な生理活性をもつインドールアルカロイド(tubifoline, olivacine)の新規合成法を開発できた。また、中枢および末梢神経に対して強い生理作用を持つABH誘導体の直接的合成法を開発できた。

Report

(4 results)
  • 2008 Annual Research Report   Final Research Report ( PDF )
  • 2007 Annual Research Report
  • 2006 Annual Research Report
  • Research Products

    (61 results)

All 2009 2008 2007 2006 Other

All Journal Article (24 results) (of which Peer Reviewed: 19 results) Presentation (35 results) Remarks (2 results)

  • [Journal Article] Reaction of Nβ-benzylserotonin with α,β-unsaturated and aryl aldehydes in the presence of a base2009

    • Author(s)
      Koji Yamada, Yuichi Namerikawa, Takumi Abe, Minoru Ishikura
    • Journal Title

      Heterocycles 77

      Pages: 825-828

    • NAID

      40016454323

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Reaction of Nb-benzylserotonin with -unsaturated and aryl aldehydes in the presence of a bas2009

    • Author(s)
      Koji Yamada
    • Journal Title

      Heterocycles 77

      Pages: 825-828

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Rhodium-catalyzed arylation of 2-azabicyclo[2.2.1]hept-5-en-3- one with arylboronic acids under microwave irradiation2008

    • Author(s)
      Takumi Abe, Hiroyuki Takeda, Yumi Takahashi, Yoshihisa Miwa, Koji Yamada, Minoru Ishikura
    • Journal Title

      Heterocycles 75

      Pages: 2931-2936

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Formal synthesis of olivacine via indolylborate2008

    • Author(s)
      Minoru Ishikura, Norinobu Takahashi, Koji Yamada, Takumi Abe, Reiko Yanada
    • Journal Title

      Helv. Chim. Acta 91

      Pages: 1828-1837

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Indium(III)-catalyzed tandem reaction with alkynylbenzaldehydes and alkynylanilines to heteroaromatic compounds2008

    • Author(s)
      Reiko Yanada, Kana Hashimoto, Rie Tokizane, Yoshihisa Miwa, Hideki Minami, Kazuo Yanada, Minoru Ishikura, Yoshiji Takemoto
    • Journal Title

      J. Org. Chem 73

      Pages: 5135-5138

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Copper-catalyzed N- arylation reaction of 2-azabicyclo[2.2.1]- hept-5-en-3-one with arylboronic acids under microwave irradiation2008

    • Author(s)
      Takumi Abe, Hiroyuki Takeda, Koji Yamada, Minoru Ishikura
    • Journal Title

      Heterocycles 76

      Pages: 133-136

    • NAID

      40016208553

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] A concise approach to (+/-)-tubifoline based on the palladium- catalyzed cross-coupling reaction of indolylborate2008

    • Author(s)
      Minoru Ishikura, Norinobu Takahashi, Koji Yamada, Takumi Abe
    • Journal Title

      Heterocycles 75

      Pages: 107-118

    • NAID

      40015919663

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] A concise approach to tubifoline based on the palladium-catalyzed cross-coupling reaction of indolylborate2008

    • Author(s)
      Minoru Ishikura
    • Journal Title

      Heterocycles 75

      Pages: 107-118

    • NAID

      40015919663

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Copper-catalyzed N-arylation of 2-azabicyclo[2.2.1]hept-5-en-3-one with arylboronic acids under microwave irradiation2008

    • Author(s)
      Minoru Ishikura
    • Journal Title

      Heterocycles 76

      Pages: 133-136

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Indium-catalyzed tandem reaction with alkynylbenzaldehydes and alkynylanilines to hetroaromatic compounds2008

    • Author(s)
      Reiko Yanada
    • Journal Title

      J. Org. Chem. 73

      Pages: 5135-5138

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Formal synthesis of olivacine via indolylborate2008

    • Author(s)
      Minoru Ishikura
    • Journal Title

      Helv. Chim. Acta 91

      Pages: 1828-1837

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Rhodium-catalyzed arylation of 2-azabicyclo[2.2.1]hept-5-en-3-one with arylboronic acids under microwave irradiation2008

    • Author(s)
      Takumi Abe
    • Journal Title

      Heterocycles 75

      Pages: 2931-2936

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A concise approach to (±) -tubifoline based on the palladium-catalyzed cross-coupling reaction of indolylborate2008

    • Author(s)
      Minoru Ishikura
    • Journal Title

      Heterocycles 75

      Pages: 107-118

    • NAID

      40015919663

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Investigation of the regioselectivity on the reaction of 2-indolylcyanocuprate with N-(prop-2-en-1-ylidene)aminium chloride derivativers2007

    • Author(s)
      Minoru Ishikura, Hiroyuki Komatsu, Koji Yamada, Takumi Abe, Reiko Yanada
    • Journal Title

      Heterocycles 71

      Pages: 2325-2329

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Investigation of the regioselectivity on the reaction of 2-indolylcyanocuprate with N-(prop-2-en-1-ylidene)aminium chloride derivatives2007

    • Author(s)
      Minoru Ishikura
    • Journal Title

      Heterocycles 71

      Pages: 2325-2329

    • NAID

      40015656004

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A palladium- catalyzed tandem cyclization-cross-coupling reaction using indolylborate as a transfer agen2006

    • Author(s)
      Minoru Ishikura, Norinobu Takahashi, Koji Yamada, Reiko Yamada
    • Journal Title

      Tetrahedron 62

      Pages: 11580-11591

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Regioselective reaction of 2-indolylcyanocuprates with electrophiles2006

    • Author(s)
      Minoru Ishikura, Reina Uemura, Koji Yamada, Reiko Yanada
    • Journal Title

      Heterocycles 68

      Pages: 2349-2356

    • NAID

      40015130013

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Microwave-assisted cycloaddition reaction of azides to N-substituted 2-azabicyclo[2.2.1]hept-5-en- 3-ones2006

    • Author(s)
      Minoru Ishikura, Miyako Hasunuma, Koji Yamada, Reiko Yanada
    • Journal Title

      Heterocycles 68

      Pages: 2253-2257

    • NAID

      40015130004

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] A one-pot access to cycloalkano[1,2-a]- indoles through an intramolecular alkyl migratiuon reaction in indolylborates2006

    • Author(s)
      Minoru Ishikura, Wataru Ida, Kazuo Yanada
    • Journal Title

      Tetrahedron 62

      Pages: 1015-1024

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] A novel synthetic application of an intramolecular alkyl migration reaction in indolylborates2006

    • Author(s)
      Minoru Ishikura
    • Journal Title

      Trends in Organic Chemistry 11

      Pages: 29-35

    • Related Report
      2008 Final Research Report
  • [Journal Article] A one-pot access to cycloaokano[1,2-a]indoles through an intramolecular alkyl migration reaction in indolylborates2006

    • Author(s)
      Minoru Ishikura
    • Journal Title

      Tetrahedron 62

      Pages: 1015-1024

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Microwave assisted cycloaddition reaction of azides to N-substituted 2-azabicyclo[2.2.1]hept-5-en-3-ones2006

    • Author(s)
      Minoru Ishikura
    • Journal Title

      Heterocycles 68

      Pages: 2253-2257

    • NAID

      40015130004

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Regioselective reaction of 2-indolylcyanocuprates with electrophiles2006

    • Author(s)
      Minoru Ishikura
    • Journal Title

      Heterocycles 68

      Pages: 2349-2356

    • NAID

      40015130013

    • Related Report
      2006 Annual Research Report
  • [Journal Article] A palladium-catalyzed tandem cyclization cross-coupling reaction using indolylborate as a transfer agent2006

    • Author(s)
      Minoru Ishikura
    • Journal Title

      Tetrahedron 62

      Pages: 11580-11591

    • Related Report
      2006 Annual Research Report
  • [Presentation] Hyrtiazepineの合成研究2009

    • Author(s)
      晴山知拓、滑川祐市、山田康司、石倉稔
    • Organizer
      日本薬学会第129年会
    • Place of Presentation
      京都
    • Year and Date
      2009-03-28
    • Related Report
      2008 Annual Research Report 2008 Final Research Report
  • [Presentation] アゼピノインドールアルカロイドの合成研究2008

    • Author(s)
      晴山知拓、滑川祐市、山田康司、阿部匠、石倉稔
    • Organizer
      日本薬学会北海道支部第131回例会
    • Place of Presentation
      小樽
    • Year and Date
      2008-11-29
    • Related Report
      2008 Annual Research Report 2008 Final Research Report
  • [Presentation] セロトニンとアルデヒドの新規環化反応を利用したアゼピノインドールアルカロイドの合成研究2008

    • Author(s)
      晴山知拓、滑川祐市、山田康司、阿部匠、石倉稔
    • Organizer
      第38回複素環化学討論会
    • Place of Presentation
      福山
    • Year and Date
      2008-11-22
    • Related Report
      2008 Final Research Report
  • [Presentation] セロトニンとアルデヒドの新規環化反応を利用したアゼピノインドールアルカロイドの合成2008

    • Author(s)
      晴山 知拓
    • Organizer
      第38回複素環化学討論会
    • Place of Presentation
      福山
    • Year and Date
      2008-11-22
    • Related Report
      2008 Annual Research Report
  • [Presentation] ジクロラミン-Tとニトリルを窒素源とするアルケンの触媒的ジアミノ化2008

    • Author(s)
      武田浩幸、阿部匠、山田康司、石倉稔
    • Organizer
      第34回反応と合成の進歩シンポジウム
    • Place of Presentation
      京都
    • Year and Date
      2008-11-04
    • Related Report
      2008 Final Research Report
  • [Presentation] ジクロラミンTとニトリルを窒素源とするアルケンの触媒的ジアミノ化反応2008

    • Author(s)
      武田 浩幸
    • Organizer
      第34回反応と合成の進歩シンポジウム
    • Place of Presentation
      京都
    • Year and Date
      2008-11-04
    • Related Report
      2008 Annual Research Report
  • [Presentation] A protocol for introduction of nucleophiles by way of indoleninium ion2008

    • Author(s)
      Yuta Kosaka
    • Organizer
      11^<th> Belgian Organic Synthesis Symposium
    • Place of Presentation
      Belgian
    • Year and Date
      2008-07-15
    • Related Report
      2008 Annual Research Report
  • [Presentation] A protocol for introduction of nucleophiles by way of indoleninium ion2008

    • Author(s)
      Yuta Kosaka, Koji Yamada, Takumi Abe, Minoru Ishikura
    • Organizer
      11^<th> Belgian Organic Synthesis Symposium
    • Place of Presentation
      Belgium
    • Year and Date
      2008-07-14
    • Related Report
      2008 Final Research Report
  • [Presentation] Chemical diversity of ABH2008

    • Author(s)
      Minoru Ishikura, Takumi Abe, Hiroyuki Takeda, Koji Yamada
    • Organizer
      11^<th> Belgian Organic Synthesis Symposium
    • Place of Presentation
      Belgium
    • Year and Date
      2008-07-14
    • Related Report
      2008 Final Research Report
  • [Presentation] Chemical Diversity of ABH2008

    • Author(s)
      Minoru Ishikura
    • Organizer
      11^<th> Belgian Organic Synthesis Symposium
    • Place of Presentation
      Belgian
    • Year and Date
      2008-07-14
    • Related Report
      2008 Annual Research Report
  • [Presentation] 銅錯体を用いたアルケンの触媒的Ritter型タンデムジアミノ化反応の開発2008

    • Author(s)
      武田浩幸、阿部匠、山田康司、石倉稔
    • Organizer
      日本薬学会北海道支部第130例会
    • Place of Presentation
      札幌
    • Year and Date
      2008-05-10
    • Related Report
      2008 Final Research Report
  • [Presentation] 銅錯体を用いたアルケンの触媒的Ritter型クンデムジアミノ化反応の開発2008

    • Author(s)
      武田 浩幸
    • Organizer
      日本薬学会北海道支部第130回例会
    • Place of Presentation
      札幌
    • Year and Date
      2008-05-10
    • Related Report
      2008 Annual Research Report
  • [Presentation] 銅錯体を用いる2-アザビシクロ[2.2.1]ヘプト-5-エン-3-オンとアリールボロン酸のクロスカップリング反応の開発2008

    • Author(s)
      武田浩幸、阿部匠、石倉稔
    • Organizer
      日本薬学会第128年会
    • Place of Presentation
      横浜
    • Year and Date
      2008-03-26
    • Related Report
      2008 Final Research Report 2007 Annual Research Report
  • [Presentation] ロジウム錯体を用いる2-アザビシクロ[2.2.1]ヘプト-5-エン-3-オンのアリール化反応の開発2008

    • Author(s)
      阿部匠、高橋有美、石倉稔
    • Organizer
      日本薬学会第128回年会
    • Place of Presentation
      横浜
    • Year and Date
      2008-03-26
    • Related Report
      2008 Final Research Report
  • [Presentation] Mannich型環化反応を用いるaurantioclavineの全合成研究2008

    • Author(s)
      滑川祐市、山田康司、石倉稔
    • Organizer
      日本薬学会第128年会
    • Place of Presentation
      横浜
    • Year and Date
      2008-03-26
    • Related Report
      2008 Final Research Report
  • [Presentation] 求核的なアルコキシド導入を経由する2-アルコキシインドール合成法の開発2008

    • Author(s)
      小坂裕太、山田康司、武田浩幸、石倉稔
    • Organizer
      日本薬学会第128年会
    • Place of Presentation
      横浜
    • Year and Date
      2008-03-26
    • Related Report
      2008 Final Research Report 2007 Annual Research Report
  • [Presentation] ロジウム錯体を用いる2-アザビシクロ[2.2.1]ヘプト-5-エン-3-オンのアリール化反応の開発2008

    • Author(s)
      石倉 稔
    • Organizer
      日本薬学会第128年会
    • Place of Presentation
      横浜
    • Related Report
      2007 Annual Research Report
  • [Presentation] Mannich型環化反応を用いるAurantioclavineの全合成研究22008

    • Author(s)
      石倉 稔
    • Organizer
      日本薬学会第128年会
    • Place of Presentation
      横浜
    • Related Report
      2007 Annual Research Report
  • [Presentation] Mannich型環化反応を用いる新規セロトニン誘導体の合成研究2007

    • Author(s)
      滑川祐市、山田康司、染井正徳、石倉稔
    • Organizer
      日本薬学会北海道支部第127回例会
    • Place of Presentation
      札幌
    • Year and Date
      2007-12-09
    • Related Report
      2008 Final Research Report
  • [Presentation] 2-アルコキシインドール類の新規合成法の開発2007

    • Author(s)
      小坂裕太、山田康司、武田浩幸、阿部匠、石倉稔
    • Organizer
      日本薬学会北海道支部第129回例会
    • Place of Presentation
      札幌
    • Year and Date
      2007-12-01
    • Related Report
      2008 Final Research Report 2007 Annual Research Report
  • [Presentation] 二環性ラクタムABHの触媒的アリール化反応の開発2007

    • Author(s)
      阿部匠、武田浩幸、高橋有美、石倉稔
    • Organizer
      第33回反応と合成の進歩シンポジウム
    • Place of Presentation
      長崎
    • Year and Date
      2007-11-05
    • Related Report
      2008 Final Research Report
  • [Presentation] 2-アルコキシインドール類の合成研究2007

    • Author(s)
      山田康司、小坂裕太、武田浩幸、阿部匠、石倉稔
    • Organizer
      第37回複素環化学討論会
    • Place of Presentation
      長野
    • Year and Date
      2007-10-18
    • Related Report
      2008 Final Research Report 2007 Annual Research Report
  • [Presentation] Investigation of the reaction of indolylcyanocuprates with iminium salts2007

    • Author(s)
      Hiroyuki Komatsu, Minoru Ishikura, Koji Yamada
    • Organizer
      21^<th> International Congress Heterocyclic Chemistry
    • Place of Presentation
      Sydney
    • Year and Date
      2007-07-17
    • Related Report
      2008 Final Research Report
  • [Presentation] Indolylborate as a building block for indole alkaloids2007

    • Author(s)
      Norinobu Takahashi, Minoru Ishikura, Koji Yamada
    • Organizer
      21th International Congress Heterocyclic Chemistry
    • Place of Presentation
      Sydney
    • Year and Date
      2007-07-17
    • Related Report
      2008 Final Research Report
  • [Presentation] Indolyl- cyanocuprateの位置選択的反応性:カルバゾール誘導体合成への展開2007

    • Author(s)
      小松弘幸、山田康司、石倉稔
    • Organizer
      日本薬学会北海道支部第128回例会
    • Place of Presentation
      札幌
    • Year and Date
      2007-05-26
    • Related Report
      2008 Final Research Report
  • [Presentation] α,β-不飽和アルデヒドとNb-ベンジルセロトニンからの新規セロトニン誘導体の合成研究2007

    • Author(s)
      滑川祐市、山田康司、染井正徳、石倉稔
    • Organizer
      日本薬学会第127年会
    • Place of Presentation
      富山
    • Year and Date
      2007-03-29
    • Related Report
      2008 Final Research Report
  • [Presentation] Indolyl- cyanocuprateを利用したカルバゾール誘導体の新規合成法の開発研究2007

    • Author(s)
      小松弘幸、山田康司、石倉稔
    • Organizer
      日本薬学会第127年会
    • Place of Presentation
      富山
    • Year and Date
      2007-03-29
    • Related Report
      2008 Final Research Report
  • [Presentation] Indolylcyanocuprateの位置選択的反応性:カルバゾール誘導体合成への展開2007

    • Author(s)
      石倉 稔
    • Organizer
      日本薬学会北海道支部第128回例会
    • Place of Presentation
      札幌
    • Related Report
      2007 Annual Research Report
  • [Presentation] Indolylborate as a building block for indole alkaloids2007

    • Author(s)
      石倉 稔
    • Organizer
      21th International Congress Heterocyclic Chemistry
    • Place of Presentation
      シドニー、オーストラリア
    • Related Report
      2007 Annual Research Report
  • [Presentation] Investigation of the reaction of indolylcyanocuprates with iminium salts2007

    • Author(s)
      石倉 稔
    • Organizer
      21th International Congress Heterocyclic
    • Place of Presentation
      シドニー、オーストラリア
    • Related Report
      2007 Annual Research Report
  • [Presentation] 二環性ラクタムABHの触媒的アリール化反応2007

    • Author(s)
      石倉 稔
    • Organizer
      第33回反応と合成の進歩シンポジウム
    • Place of Presentation
      長崎
    • Related Report
      2007 Annual Research Report
  • [Presentation] インドリルボレートを用いるドミノ型クロスカップリング反応2006

    • Author(s)
      高橋法伸、山田康司、石倉稔
    • Organizer
      第32回反応と合成の進歩シンポジウム
    • Place of Presentation
      広島
    • Year and Date
      2006-12-04
    • Related Report
      2008 Final Research Report
  • [Presentation] 新規テトラヒドロ-1H-アゼピノ[5.4.3-cd]インドール化合物の合成とアルカロイド合成への展開2006

    • Author(s)
      山田康司、染井正徳、石倉稔
    • Organizer
      第36回複素環化学討論会
    • Place of Presentation
      長崎
    • Year and Date
      2006-11-23
    • Related Report
      2008 Final Research Report
  • [Presentation] indolylcyanocuprateを用いる2,3-ジ置換インドールの新規合成2006

    • Author(s)
      小松弘幸、上村怜奈、山田康司、石倉稔
    • Organizer
      第36回複素環化学討論会
    • Place of Presentation
      長崎
    • Year and Date
      2006-11-23
    • Related Report
      2008 Final Research Report
  • [Presentation] Palladium-catalyzed tandem cyclization-cross-coupling reaction of indolylborate

    • Author(s)
      Norinobu Takahashi, Minoru Ishikura
    • Organizer
      16^<th> International Conference on Organic Synthesis
    • Related Report
      2008 Final Research Report
  • [Remarks]

    • URL

      http://www.hoku-iryo-u.ac.jp./~iyaku/

    • Related Report
      2008 Annual Research Report
  • [Remarks]

    • URL

      http://www.hoku-iryo-u.ac.jp/~iyaku/

    • Related Report
      2007 Annual Research Report

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Published: 2006-04-01   Modified: 2016-04-21  

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